Microfluidic structures allow liquid volumes to be manipulated on a very small scale, in the nanoliter range. This has many benefits for biological sampling and testing, such as the reduced consumption of samples and reagents, shorter analysis times, greater sensitivity and ease of transportation and disposal. Initially such systems were made using glass or silicon, as methods of manufacturing with these materials were known from the microelectronics industry. Channels were created by, e.g., photo lithography, wet etching or micromachining, after which the channels were sealed by a layer of the same material using anodic bonding, fusion bonding or adhesives.
However, glass and silicon are not best suited to the biomedical field as they are expensive, can lack optical clarity, have a low impact strength and poor biocompatibility. Therefore there has been a move away from these materials towards plastics. These offer a wide range of physical and chemical characteristics. A discussion of various methods of manufacture of polymer microfluidic devices can be found in Polymer Microfluidic Devices by Holger Becker and Laurie Locascio (Talanta 56 (2002) 267-287).
One of the methods discussed is that of injection moulding using compact disc (CD) manufacturing technology. Here a master is made from silicon using wet chemical etching or deep reactive ion etching. Nickel electroforms are then produced from the silicon master in order to transfer the micro features to a substrate suitable for injection moulding. The nickel electroform is then mounted onto a mould insert and thermoplastic resin is introduced to form the microchannels. These are later sealed to a polymer substrate of the same type or one with a lower glass transition temperature using low temperature thermal annealing.
Alternative ways of forming microchannels are by imprinting or hot embossing.
Recently elastomers have gained popularity in the field of microfluidic devices due to their flexibility. This allows channels in the elastomer to be closed by the application of pressure to the elastomer, which distorts the shape of the channels. By having a series of layered channels fluid movement in one channel can be controlled by the application of pressurised air to channels positioned above it. This allows microfluidic devices to be fashioned with inbuilt pumps or valves and allows the controlled dispensing or movement of fluid within the device. Poly(dimethylsiloxane) (PDMS) has emerged as a useful elastomer for rapid prototyping of microfluidic structures as it is inexpensive, easy to replicate by moulding and is optically transparent. In addition, PDMS has a high oxygen and carbon dioxide permeability which permits cells located in the microchannels to maintain aerobic metabolism. This is a major difference over conventional plastic, glass and silicon devices which do not allow for gas exchange and are therefore not suited for cell based applications.
WO02/43615 discloses several methods of manufacturing a microfluidic device Lasing elastomers, in particular PDMS.
First moulds are micromachined Lasing conventional techniques, e.g. photolithography, to create the microchannels in relief. Uncured elastomer is placed over the mould and allowed to cure to form microchannels. The elastomer can them be bonded to a substrate or to another piece of elastomer to seal the channels.
Several methods of bonding elastomer to elastomer are discussed, including a reference to Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane) by Duffy et al (Anal. Chem. 1998, 70, 4974-4984). This discloses a method for making PDMS microfluidic systems by first creating a master by photolithography of a silicon wafer. Glass posts are then placed in the master to define reservoirs for liquids. Uncured PDMS is cast over the master and cured. This is achieved by heating the PDMS to around 65° C. for 1 hour. After curing, the PDMS is removed from the master and the glass posts are removed. In order to seal the channels a second, flat layer of PDMS is used. Both PDMS elements are oxidised and then brought into contact. The oxidation converts —OSi(CH3)2O— groups at the surface to —OnSi(OH)4-n. This is believed to result in the formation of bridging, covalent siloxane (Si—O—Si) bonds, which forms an irreversible seal between the PDMS layers.
Duffy et al also state that PDMS seals irreversibly to glass, silicon, silicon oxide, quartz, silicon nitrate, polyethylene, polystyrene and glassy carbon after cleaning and exposing both surfaces to an oxygen plasma.
The method laid out in Duffy proposes a means of manufacture of microfluidic devices in under 24 hours. Reduction in the time taken to make the devices is limited by the time taken to mould and cure the elastomer.
In contrast to PDMS devices, thermoplastic microchannels can be made in a matter of seconds due to the high throughput injection moulding techniques available. However, the sealing means for such channels are not so sophisticated. The techniques used (thermal annealing, adhesive tape, solvent bonding) all tend to deform the microstructures and often introduce materials unsuitable for the intended application, such as toxic solvents or highly autofluorescent adhesives. Moreover, as these materials are inflexible, mechanical pumping is not possible and other techniques, such as electro-osmotics, must be relied on.
WO02/43615 discloses the bonding of an elastomer to a non-elastomer substrate containing recesses which form microfluidic channels. This can be done by creating microchannels in the substrate using traditional methods, filling the channels with sacrificial material, coating the substrate with uncured elastomer, curing the elastomer and finally removing the sacrificial material. However, this technique still includes a time delay while the elastomer is cured.
Other bonding methods disclosed use Van der Waals, covalent and ionic bonds. Covalent bonding is described in relation to the bonding of glass to a silicone elastomer and requires the glass substrate to first be exposed to agents such as vinyl silane or aminopropyltrithoxy silane. The other examples given also relate to glass substrates which, as mentioned previously, are not suited to the field of biomedical applications.
Therefore there still exists a need for a cheap, easy to manufacture microfluidic structure which is suited to use in the biomedical and biochemical fields.